B-cell depletion with anti-CD20 monoclonal antibody (mAb) represents a novel and highly effective treatment for patients with multiple sclerosis. Although all approved anti-CD-20 mAbs for multiple sclerosis (MS) treatment, ocrelizumab, ofatumumab, and ublituximab, target the same molecule on the B-cell surface, some differences in their molecular structure translate into important distinctions in their mechanisms of B-cell depletion. Differences between an antibody-dependent cell-mediated cytotoxicity (ADCC) versus a complement-dependent cytotoxicity (CDC) in anti-CD20 mAbs mechanism of action correspond to deeper B-cell depletion as well as better tolerability. Glycoengineering of the Fc portion of ublituximab with reduced fucosylation enhances affinity to Fc gamma receptor IIIa (FcγRIIIa) on natural killer (NK) cells. This molecular modification of ublituximab exhibits significantly higher ADCC activity in relation to CDC in B-cell depletion mechanisms. In addition, glycoengineering of ublituximab reduces the importance of the FcγRIIIa 158V/F polymorphism, which influences the effectiveness of B-cell depletion. In the ULTIMATE I and II studies, ublituximab showed a significant reduction in annual relapse rate versus teriflunomide in relapsing MS patients and strikingly reduced active and new/enlarging MRI lesions. Ublituximab also showed efficacy on the disease progression and increased disability improvement in the extended 5-year observation study. The advantage of ublituximab also correlates with good tolerability and reduced infusion-related reactions. Ublituximab infusion, 1 h, is significantly shorter in comparison to other intravenous (IV) preparations of anti-CD20 mAbs. Thus, ublituximab provides better convenience to MS patients as well as saves the time of healthcare providers.
Selmaj et al. (Sun,) studied this question.